title: Vaccine-elicited SIV and HIV envelope-specific IgA and IgG memory B cells in rhesus macaque peripheral blood correlate with functional antibody responses and reduced viremia.
abstract: An effective HIV vaccine requires strong systemic and mucosal, cellular and humoral immunity. Numerous non-human primate studies have investigated memory T cells, but not memory B cells. Humoral immunologic memory is mediated by long-lived antibody-secreting plasma cells and differentiation of memory B cells into short-lived plasma blasts following re-exposure to immunizing antigen. Here we studied memory B cells in vaccinated rhesus macaques. PBMC were stimulated polyclonally using CD40 Ligand, IL-21 and CpG to induce B cell proliferation and differentiation into antibody secreting cells (ASCs). Flow cytometry was used for phenotyping and evaluating proliferation by CFSE dilution. B cell responses were quantified by ELISPOT. Methodology was established using PBMC of vaccinated elite-controller macaques that exhibited strong, multi-functional antibody activities. Subsequently, memory B cells elicited by two replicating Ad-recombinant prime/envelope boost regimens were retrospectively evaluated pre- and post-SIV and SHIV challenges. The vaccine regimens induced SIV and HIV Env-specific IgG and IgA memory B cells. Prior to challenge, IgA memory B cells were more numerous than IgG memory B cells, reflecting the mucosal priming immunizations. Pre- and post-challenge memory B cells were correlated with functional antibody responses including antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cell-mediated viral inhibition (ADCVI) and transcytosis inhibition. Post-challenge, Env-specific IgG and IgA memory B cells were correlated with reduced chronic viremia. We conclude that functional antibody responses elicited by our prime/boost regimen were effectively incorporated into the memory B cell pool where they contributed to control of viremia following re-exposure to the immunizing antigen.
authors.affiliation: Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: Egidio
authors.initials: E
authors.lastname: Brocca-Cofano
authors.forename: Katherine
authors.initials: K
authors.lastname: McKinnon
authors.forename: Thorsten
authors.initials: T
authors.lastname: Demberg
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.forename: Rachmat
authors.initials: R
authors.lastname: Hidajat
authors.forename: Peng
authors.initials: P
authors.lastname: Xiao
authors.forename: Mara
authors.initials: M
authors.lastname: Daltabuit-Test
authors.forename: L Jean
authors.initials: LJ
authors.lastname: Patterson
authors.forename: Marjorie
authors.initials: M
authors.lastname: Robert-Guroff
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay; D005434:Flow Cytometry; D006678:HIV / Q000276:immunology*; D007070:Immunoglobulin A / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood*; D007156:Immunologic Memory; D008253:Macaca mulatta; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*; D014766:Viremia / Q000517:prevention & control*
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D014759:Viral Envelope Proteins